An approach to cyclic peptide libraries: Reducing epimerization in medium sized rings during solid phase synthesis

Spatola, Arno F.; Darłak, Krzysztof; Romanovskis, Peteris

doi:10.1016/0040-4039(95)02269-4

Cited by 52 publications

(29 citation statements)

References 15 publications

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“…Alternative linkers used in this approach include thioesters [46], 'safety-catch' linkers based on sulfonamide [47], or the most recent catechol example [48] summarized in Scheme 4. A totally on-resin approach has been developed by linking the side chain of a trifunctional amino acid to the resin, and through use of three levels of orthogonal protection, a protocol such as the one depicted in Scheme 5 [49,50] has proved successful. Many aspects of this on-resin approach have been reviewed authoritatively by Spatola and Romanovskis [25].…”

Section: On-resin Cyclizationsmentioning

confidence: 99%

The cyclization of peptides and depsipeptides

Davies

2003

Journal of Peptide Science

414

241

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Constricting the peptide backbone into a more defined conformational form through cyclization is an activity evolved in nature and in synthetic work, the latter straddling only the most recent decades. The resulting conformational constraints increase the probability of an optimum response with bio-receptors. The purpose of this review is to highlight developments that have proved to be reasonably efficient in the macrocyclization of linear precursors into cyclic peptides and depsipeptides.

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Section: On-resin Cyclizationsmentioning

confidence: 99%

The cyclization of peptides and depsipeptides

Davies

2003

Journal of Peptide Science

414

241

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“…For the optimization of reaction conditions, we selected the model compound α‐guanidino‐glutaryl‐leucine, synthesized on Merrifield resin. Among different cyclization reagents, described in the literature28–30, DIC/HOBt seems appropriate for this case. The guanidinylation was performed using Boc 2 CABt/DIEA in accordance with procedure for synthesis of peptides containing N ‐amidino‐proline12.…”

Section: Resultsmentioning

confidence: 99%

Incorporation of N‐amidino‐pyroglutamic acid into peptides using intramolecular cyclization of α‐guanidinoglutaric acid

Буров

Moskalenko

Dorosh

et al. 2009

Journal of Peptide Science

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N-terminal modification of peptides by unnatural amino acids significantly affects their enzymatic stability, conformational properties and biological activity. Application of N-amidino-amino acids, positively charged under physiological conditions, can change peptide conformation and its affinity to the corresponding receptor. In this article, we describe synthesis of short peptides, containing a new building block-N-amidino-pyroglutamic acid. Although direct guanidinylation of pyroglutamic acid and oxidation of N-amidino-proline using RuO(4) did not produce positive results, N-amidino-Glp-Phe-OH was synthesized on Wang polymer by cyclization of alpha-guanidinoglutaric acid residue. In the course of synthesis, it was found that literature procedure of selective Boc deprotection using TMSOTf/TEA reagent is accompanied by concomitant side reaction of triethylamine alkylation by polymer linker fragment. It should be mentioned that independently from cyclization time and coupling agent (DIC or HCTU), the lactam formation was incomplete. Separation of the cyclic product from the linear precursor was achieved by HPLC in ammonium formate buffer at pH 6. HPLC analysis showed N-amidino-Glp-Phe-OH stability at acidic and physiological pH and fast ring opening in water solution at pH 9. The suggested method of N-amidino-Glp residue formation can be applied in the case of short peptide chains, whereas synthesis of longer ones will require fragment condensation approach.

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“…Also, immobilization of Asp and Glu on bromomethyl resin 5.1 [186], HMPA resin 2.6 [186], PAL linker 2.18 [187,188], hydroxymethyl resin 5.2 [189][190][191], and tris (methoxy)benzhydrylamine (TMBPA) linker 5.3 [192] have been described (Figure 8.9). Side-chain immobilization of Lys (and any other amino acids with amino groups in their side-chains, such as ornithine, homolysine, etc.)…”

Section: Carboxyl Groupmentioning

confidence: 99%